Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

AMP-Activated Protein Kinases/*metabolism ; Endometrium/*immunology ; Endometrium/*metabolism ; Energy Metabolism/*drug effects ; Glucose/*pharmacology ; Immunity, Innate/*drug effects; Animals ; Cattle ; Endometrium/drug effects ; Endometrium/pathology ; Female ; Inflammation/pathology ; Insulin-Like Growth Factor I/metabolism ; Lipopolysaccharides ; Phosphorylation ; Stress, Physiological/drug effects ; TOR Serine-Threonine Kinases/metabolism

Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity.

Domest Anim Endocrinol. 2015 Jan;50:83-90. (PMID: 25447883)
Cell Metab. 2012 Jun 6;15(6):813-26. (PMID: 22682222)
Science. 2000 Nov 10;290(5494):1166-8. (PMID: 11073456)
Biol Reprod. 1997 Mar;56(3):608-16. (PMID: 9047004)
Endocrinology. 2006 Jan;147(1):562-70. (PMID: 16223858)
J Dairy Sci. 2007 Sep;90(9):4022-32. (PMID: 17699018)
Domest Anim Endocrinol. 2008 May;34(4):391-402. (PMID: 18258405)
Nature. 2008 Jul 24;454(7203):428-35. (PMID: 18650913)
Nat Rev Immunol. 2008 Dec;8(12):923-34. (PMID: 19029988)
Vet Immunol Immunopathol. 2008 Dec 15;126(3-4):199-210. (PMID: 18692908)
J Biol Chem. 2009 Mar 20;284(12):8023-32. (PMID: 19150980)
Science. 2009 May 22;324(5930):1029-33. (PMID: 19460998)
Reprod Biol Endocrinol. 2009;7:55. (PMID: 19476661)
J Dairy Sci. 2009 Sep;92(9):4301-16. (PMID: 19700690)
Physiol Genomics. 2009 Sep 9;39(1):1-13. (PMID: 19567787)
Biol Reprod. 2009 Dec;81(6):1025-32. (PMID: 19439727)
PLoS One. 2010;5(2):e9192. (PMID: 20169203)
Cell. 2010 Mar 19;140(6):805-20. (PMID: 20303872)
Endocrinology. 2010 Jun;151(6):2846-57. (PMID: 20351317)
J Clin Invest. 2001 Oct;108(8):1167-74. (PMID: 11602624)
J Dairy Sci. 2002 Mar;85(3):537-43. (PMID: 11949857)
Reproduction. 2002 Jun;123(6):837-45. (PMID: 12052238)
J Reprod Fertil. 1972 Apr;29(1):133-6. (PMID: 5062845)
J Anim Sci. 1992 May;70(5):1496-508. (PMID: 1526919)
FEBS Lett. 1994 Oct 10;353(1):33-6. (PMID: 7926017)
Cell Death Dis. 2012;3:e357. (PMID: 22833096)
Vet Microbiol. 2012 Oct 12;159(3-4):460-9. (PMID: 22595139)
Nature. 2013 Jan 17;493(7432):346-55. (PMID: 23325217)
Nature. 2013 Apr 11;496(7444):238-42. (PMID: 23535595)
J Dairy Sci. 2013 Jun;96(6):3621-31. (PMID: 23548288)
Anim Reprod Sci. 2014 Jan 30;144(3-4):60-71. (PMID: 24378117)
Biol Reprod. 2014 Mar;90(3):54. (PMID: 24478394)
Endocrinology. 2014 Apr;155(4):1453-65. (PMID: 24437488)
Reproduction. 2014 Dec;148(6):593-606. (PMID: 25246618)
Blood. 2010 Jun 10;115(23):4742-9. (PMID: 20351312)
Science. 2010 Dec 3;330(6009):1340-4. (PMID: 21127244)
Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35. (PMID: 21157483)
Reprod Biol Endocrinol. 2010;8:152. (PMID: 21176181)
Reproduction. 2011 Feb;141(2):269-81. (PMID: 21123519)
Trends Endocrinol Metab. 2011 Mar;22(3):94-102. (PMID: 21269838)
Nat Immunol. 2011 Apr;12(4):295-303. (PMID: 21358638)
Curr Biol. 2011 Jul 12;21(13):R488-93. (PMID: 21741580)
Nat Immunol. 2011 Aug;12(8):742-51. (PMID: 21725320)
Reproduction. 2011 Aug;142(2):211-20. (PMID: 21642384)
Nat Cell Biol. 2011 Sep;13(9):1016-23. (PMID: 21892142)
Biol Reprod. 2012 Feb;86(2):51. (PMID: 22053092)
Nat Rev Mol Cell Biol. 2012 Apr;13(4):251-62. (PMID: 22436748)
Am J Reprod Immunol. 2012 Jun;67(6):526-39. (PMID: 22324889)
J Immunol. 2016 Jan 15;196(2):823-31. (PMID: 26673142)

BB/F005121/2 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/I017240/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council

0 (Lipopolysaccharides)
67763-96-6 (Insulin-Like Growth Factor I)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
IY9XDZ35W2 (Glucose)

Date Created: 20160315 Date Completed: 20160808 Latest Revision: 20220129

20231215

PMC4790959

10.1371/journal.pone.0151416

26974839